Antidepressant discontinuation-related mania: Critical prospective observation and theoretical implications in bipolar disorder

Background: Development of manic symptoms on antidepressant discontinuation has primarily been reported in unipolar patients. This case series present s preliminary evidence for a similar phenomenon in bipolar patients. Method: Prospectively obtained life chart ratings of 73 bipolar patients at the National Institute of Mental Health were reviewed for manic episodes t hat emerged during antidepressant taper or discontinuation. Medical records were utilized as a corroborative resource. Six cases of antidepressant dis continuation-related mania were identified and critically evaluated. Results: All patients were taking conventional mood stabilizers. The patien ts were on antidepressant treatment a mean of 6.5 months prior to taper, wh ich lasted an average of 20 days (range, 1-43 days). First manic symptoms e merged, on average, 2 weeks into the taper (range, 1-23 days). These 6 case s of antidepressant discontinuation-related mania involved 3 selective sero tonin reuptake inhibitors (SSRIs), 2 tricyclic antidepressants (TCAs), and 1 serotonin-norepinephrine reuptake inhibitor. Mean length of the ensuing m anic episode was 27.8 days (range, 12-49 days). Potential confounds such as antidepressant induction, phenomenological misdiagnosis of agitated depres sion, physiologic drug withdrawal syndrome, and course of illness were care fully evaluated and determined to be noncontributory. Conclusion: These 6 cases suggest a paradoxical effect whereby antidepressa nt discontinuation actually induces mania in spite of adequate concomitant mood-stabilizing treatment. These preliminary observations, if replicated i n larger and controlled prospective studies, suggest the need for further c onsideration of the potential biochemical mechanisms involved so that new p reventive treatment approaches can be assessed.